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標題: | 預測vancomycin臨床療效之最適指標:谷藥品濃度或曲線下面積/最低抑菌濃度? The Most Appropriate Parameter Correlates with Clinical Effectiveness of Vancomycin: Trough Drug Concentration or AUC/MIC? |
作者: | Hsing-Yu Lin 林星羽 |
指導教授: | 沈麗娟(Li-Jiuan Shen) |
關鍵字: | 萬古黴素,AUC/MIC比值,谷藥品濃度,療劑監測,藥動學,藥效學, Vancomycin,AUC/MIC ratio,trough concentration,therapeutic drug monitoring,pharmacokinetics,pharmacodynamics, |
出版年 : | 2014 |
學位: | 碩士 |
摘要: | 研究背景
萬古黴素(vancomycin)為治療抗藥性金黃色葡萄球菌(MRSA)感染症之首選抗生素,臨床上可以進行療劑監測(therapeutic drug monitoring, TDM)達到適當療效。目前治療指引建議臨床上採用谷藥品濃度(trough concentration, Ctrough)做為監測指標,但有文獻指出vancomycin血中濃度對時間之曲線下面積(AUC)/最低抑菌濃度(MIC)比值才是能準確預測vancomycin治療結果的參數。隨著近年研究指出Ctrough和AUC/MIC的相關性不如預期,確認哪一種參數最能預測vancomycin臨床療效並且應用於臨床實務中是重要的議題。 研究目的 (1)驗證AUC/MIC是否更適於Ctrough預測vancomycin臨床治療效果、(2)評估華人是否適用國外文獻中的群體藥動學公式來預測vancomycin療效,(3)探討vancomycin Ctrough和AUC/MIC相關性。 研究設計與方法 本研究回溯性觀察西元2001年至2011年臺大醫院急診就醫確診MRSA菌血症、並且在血液培養後3日內開始vancomycin靜脈注射治療、治療大於3日以上達血中濃度穩定而進行療劑監測之非透析病人。以邏輯斯迴歸分析vancomycin Ctrough和以群體藥動學公式計算之AUC/MIC兩者分別與30日存活結果之關聯性,並以分類迴歸分析方法(CART)、ROC曲線評估各公式計算之AUC/MIC對30日存活結果預測力。 研究結果 一共432位急診就醫確診MRSA菌血症病人,排除196位vancomycin用藥資料不足、83位進行血液透析病人、30位vancomycin用藥時間不符研究條件,最終共123人進入分析。平均年齡63 ± 17歲,男性比例57%,30日死亡人數為19人(15.4%)。分析結果顯示Ctrough於30日存、亡兩組間無統計顯著差異(12.2 ± 5.7 v.s. 14.4 ± 7.5 mg/L, p=0.32),而群體藥動學公式計算之AUCRodvold /MICEtest是最具30日存亡預測力、在30日存活組中統計顯著較高(334.6 ± 124.6 vs. 258.1 ± 124.1; p=0.01)。AUCRodvold /MICEtest≧220經多變項迴歸分析後,與30日死亡顯著負相關(aOR=0.27, 95% CI 0.09-0.83, p=0.02)。此外也觀察到Ctrough和AUCRodvold、AUCRodvold /MICEtest之間並無良好的線性關係(依序為r=0.451, p<0.01; r=0.27, p<0.01)。 結論 以群體藥動學公式計算之AUC/MIC比Ctrough更適合預測vancomycin臨床療效,其中以AUCRodvold /MICEtest≧220最具預測力。建議臨床進行vancomycin療劑監測時,應使用AUC/MIC做為監測指標,而非Ctrough。未來可進行前瞻性隨機之臨床試驗進一步確認本研究的結果。 Background Vancoymycin is an important antibiotic for the treatment of methicillin resistant Staphylococcus aureus (MRSA). Trough concentration (Ctrough) of vancomycin has been used as a pharmacokinetic/pharmacodynamic (PK/PD) parameter in therapeutic drug monitoring to ensure the outcome of the treatment for years. However, some studies showed that the ratio of area under the curve of vancomycin and minimum inhibitory concentration of the bacteria (AUC/MIC) was a better indicator for PK/PD of vancomycin in clinical practice. In addition, poor relation between Ctrough and AUC/MIC of vancomycin has been demonstrated. It is an important issue to clarify which is the most appropriate parameter correlated with clinical effectiveness of vancomycin in patients with infection of MRSA. Objectives This study was to (1) determine which parameter, AUC/MIC or Ctrough, have a better association with the outcome of vancomycin, (2) validate that calculated AUC/MIC by using population equation can be used to predict vancomycin clinical effectiveness in Chinese population, and (3) evaluate the correlation between vancomycin Ctrough and calculated AUC/MIC. Materials and Methods This retrospective cohort study was conducted in the Emergency Department of National Taiwan University Hospital. Non-dialysis patients diagnosed with MRSA bacteremia receiving vancomycin therapy in 3 days after positive blood culture and undergoing therapeutic drug monitoring between 2001 and 2011 were included. AUC/MICs of vancomycin were calculated with published equations and Ctrough were retrieved from medical charts. Subsequetnly, the association of 30-day all-cause mortality and PK/PD parameters was analyzed with receiver operating characteristic curve (ROC) and logistic regression. Cut-off point of AUC/MICs associated with reduced 30-day all-cause mortality was derived using classification and regression tree analysis (CART). Results Total 432 patients diagnosed with MRSA bacteremia were included. Three hundred and nine of these patients were excluded (196 patients, insufficient data about vancomycin dosing and serum concentration; 83 patients, undergoing dialysis; 30 patients, delayed vancomycin therapy or shorter than 3 days), leaving 123 patients for final analysis. Ninteen of 123 (15.4%) patients expired in 30 days. No significant difference was observed in Ctrough between two groups (12.2 ± 5.7 v.s. 14.4 ± 7.5 mg/L, p=0.32). However, calculated AUC/MICs using vancomycin clearance derived from Rodvold equation and MIC value of E-test (AUCRodvold /MICEtest), the best method to predict 30-day outcome in our study, was significantly different between 30-day survivors and non-survivors (334.6 ± 124.6 vs. 258.1 ± 124.1; p=0.01). AUCRodvold /MICEtest above 220 was associated with reduced mortality and remained significant in a multivariable model (aOR=0.27, 95% CI 0.09-0.83, p=0.02). Poor linear relations between Ctrough and both of AUCRodvold and AUCRodvold /MICEtest were also observed (r=0.451, p<0.01; r=0.27, p<0.01, respectively). Conclusions Calculated AUC/MIC is a better parameter which associates with clinical effectiveness of vancomycin compared to the Ctrough. AUCRodvold /MICEtest≧220 can be used as a target to improve clinical effectiveness of vancomycin in clinical practice. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/56712 |
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